eMedicine Specialties > Dermatology > Benign Neoplasms

Congenital Self-Healing Reticulohistiocytosis

Author: David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
Coauthor(s): Jessica L Clark, MD,, Texas A&M University System Health Science Center College of Medicine
Contributor Information and Disclosures

Updated: Dec 10, 2008

Introduction

Background

Langerhans cell histiocytosis (LCH), once described as histiocytosis X, is a clonal proliferative disorder of Langerhans cells that stain immunohistochemically with S-100 and CD-1a and demonstrate cytoplasmic Birbeck granules under electron microscopy.¹  Four variants of this disorder have been described: Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma, and congenital self-healing reticulohistiocytosis (CSHR), also termed Hashimoto-Pritzker disease.²

Letterer-Siwe disease is an acute, sometimes fulminant, multisystem disorder that commonly develops during early infancy. Skin findings often demonstrate multiple scaly papules in a seborrheic distribution. Lesions occur in crops and may be crusted or hemorrhagic. Systemic involvement may include the pulmonary system, the liver, the spleen, bone, bone marrow, the hypothalamus, the gastrointestinal tract, and lymph nodes.³   

Hand-Schüller-Christian disease is a chronic, progressive, multifocal variant that usually affects adults. This variant has 4 characteristic findings: exophthalmos, diabetes insipidus, bone lesions, and mucocutaneous lesions. Skin lesions often have a xanthomatous appearance.⁴

Eosinophilic granuloma is a more chronic, localized disorder that most often involves bone. The cranium, ribs, vertebrae, pelvis, scapulae, and long bones may be involved.² Related eMedicine articles include Eosinophilic Granuloma (Histiocytosis X), Eosinophilic Granuloma, Skeletal, and Eosinophilic Granuloma, Thoracic.

Congenital self-healing reticulohistiocytosis was first reported in 1973 by Hashimoto and Pritzker as a benign, self-limited variant of LCH with only skin involvement.⁵ This variant usually manifests at birth or during the neonatal period as reddish-brown papules or papulovesicular lesions. Lesions resolve within 3 months. Systemic involvement does not develop.

Because skin manifestations of the more aggressive, systemic forms of LCH may initially be lesions that mimic congenital self-healing reticulohistiocytosis, a thorough evaluation for systemic abnormalities must be undertaken. Congenital self-healing reticulohistiocytosis is truly a diagnosis of exclusion, and long-term follow-up monitoring for possible relapse or progression of the disease is required.

eMedicine articles on related topics include Multicentric Reticulohistiocytosis and Langerhans Cell Histiocytosis.

Pathophysiology

Langerhans cells arise from bone marrow precursors to populate the epidermis and act as antigen-presenting cells; they play a key role in immune surveillance and contact sensitivity. The clonal, proliferative nature of LCH has long been debated as to whether it represents a reactive or neoplastic process.⁶ A virally induced proliferation of Langerhans cells was disproved by extensive polymerase chain reaction screening for 9 different viruses.⁷

Elevated levels of cytokines such as tumor necrosis factor-alpha; interferon gamma; granulocyte-monocyte colony-stimulating factor; and interleukins 1, 2, 4, and 10 have been demonstrated in  the tissue of LCH lesions.^8,9 The actual role of these cytokines in the pathogenesis of the disease remains obscure.

Frequency

United States

Owing to the high rate of spontaneous resolution and lack of clinical recognition, the true incidence of congenital self-healing reticulohistiocytosis may be underreported.¹⁰ The reported prevalence of LCH in children is 5 cases per million population,² and the incidence rate of congenital self-healing reticulohistiocytosis is much lower.

International

An annual prevalence of 4-5.4 cases per million population is reported for all forms of LCH, and, since Hashimoto and Pritzker first described congenital self-healing reticulohistiocytosis in 1973, more than 100 cases have been reported.

Mortality/Morbidity

Congenital self-healing reticulohistiocytosis has been regarded as the benign end of the spectrum of LCH. By definition, congenital self-healing reticulohistiocytosis is a self-limited disorder and clinical features should completely resolve over a period of months. The few reports of relapses or the development of systemic LCH after a diagnosis of congenital self-healing reticulohistiocytosis actually represent systemic disease that initially manifested in a manner similar to congenital self-healing reticulohistiocytosis.

Race

The prevalence of LCH seems to be higher among whites than persons of other races.

Sex

The sex distribution is equal.

Age

The cutaneous lesions of congenital self-healing reticulohistiocytosis typically manifest at birth or during the first 2 months of life. One case report documents the presentation of an 8-year-old girl in Japan who had multiple asymptomatic, reddish-brown papules over her face and upper limbs.¹¹ Skin lesions normally resolve over a 3- to 4-month period.

New papules that develop after age 2 months  are not typical of congenital self-healing reticulohistiocytosis and should be investigated as possibly being a more aggressive form of LCH. Aggressive forms of LCH may manifest during the neonatal period.

The Medscape Pediatric Dermatology Resource Center may be of interest.

Clinical

History

Skin lesions typically are present at birth or develop during the neonatal period. Papules are most often asymptomatic. Most commonly, a history of a normal delivery following a normal-term pregnancy is reported. In one report, urticaria developed a few days after the development of the papules.¹² See Media File 1.

Physical

The development of multiple reddish-brown papules is the most common presentation of congenital self-healing reticulohistiocytosis (see Media Files 1-2). Solitary lesions are reported in 25% of the cases.^13,14 Papules tend to be located on the head, neck, and distal extremities. The papules may become crusted.¹⁵

Other manifestations may include vesicles, pustules, plaques, scaling patches, blue nodular skin infiltrates, hemorrhagic bullae, and hemangiomalike lesions.^16,17,18,19 One case of intense residual pigmentation (due to hemosiderin deposition) at the sites of resolving skin lesions has been reported.²⁰

Eye involvement that resolved concurrently with the skin lesions has been reported.²¹ Additionally, one infant with congenital self-healing reticulohistiocytosis demonstrated multiple lung cysts that completely resolved within 1 year.²² Finally, although hepatomegaly has been noted in some infants, the clinical significance of this is uncertain.

The lesions of congenital self-healing reticulohistiocytosis have been reported to urticate after physical manipulation (pseudo-Darier sign); this occurs because of  the increased numbers of mast cells in lesional skin along with the Langerhans cells.¹²

Particular attention should be given during examination to look for signs of extracutaneous involvement, such as the following:

• Lymphadenopathy
• Hepatosplenomegaly
• Soft tissue mass
• Neurologic deficits
• Pathologic fractures

The skin lesions of congenital self-healing reticulohistiocytosis may be localized or widely disseminated. Although a solitary lesion or a limited number of lesions is more common, disseminated crusted papules of congenital self-healing reticulohistiocytosis have been reported.²³ The papules often heal with a depressed chickenpoxlike scar.

Causes

The etiology of congenital self-healing reticulohistiocytosis remains unknown. Viral, neoplastic, and immunologic mechanisms have been proposed. Elevated values of cytokines, including interleukins 1 and 2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, have been reported, suggesting the possibility of deregulated immune stimulation.²⁴

• Search for CME/CE on This Topic »